Bioinspired Framework Nucleic Acid Capture Sensitively and Rapidly Resolving MicroRNAs Biomarkers in Living Cells
Fan Yang, Yaru Cheng, Yiyi Zhang, Wei Wei, Haifeng Dong, Huiting Lu, Xueji Zhang
Abstract
Quantifying intracellular microRNA (miRNA) is essential for diagnosis and prognosis of diseases because of its importance to the development and progression of complex diseases. The challenge is to develop methods that enable multiplex miRNAs detection in ultralow amounts and over broad concentration ranges. Inspired by the "tentacles" of an octopus, herein, we present a framework nucleic acid (FNA) capture for sensitive, rapid, and multiplexed imaging of miRNAs cancer biomarkers in living cells. The programmable FNA is designed using three DNA triangular prism (DTP) nanostructures carrying two pairs of metastable catalytic hairpin assembled (CHA) probes, AS1411 aptamer, and pendent biotinylated DNA strand in different vertexes and is further assembled via streptavidin to form the multivalent DTP (SA-DTP). The SA-DTP system acts as an octopus that captures the target cancer miRNAs quickly and delivers them preferentially among DTPs' "tentacles" in the SA-DTP system to produce strong, amplified fluorescence for detection. Precise multiplexed imaging of miRNA-155 and miRNA-21 cancer biomarkers' aberrant expression and dynamic change in different cells demonstrates the feasibility of both monitoring disease progression and evaluating therapeutic efficacy.